Inmunorreactividad antineural sérica en pacientes con fibromialgia. Estudio preliminar / Serum anti-neural immunoreactivity in patients with fibromyalgia. Preliminary study

Resumen Introducción: La fibromialgia (FM) es un síndrome no degenerativo caracterizado por dolor musculoesquelético crónico y generalizado; así como por alteraciones anímicas, de memoria y sueño. Objetivo: Buscar anticuerpos antineurales (AANeu) séricos en pacientes con FM para descartar etiología autoinmune. Métodos: Se aplicó el Cuestionario de Impacto en Fibromialgia (FIQ) y el Inventario de Depresión de Beck (BDI). La inmunorreactividad y el blanco reconocido por los sueros de pacientes con FM y sujetos sanos se analizó con inmunofluorescencia indirecta y Western blot. Resultados: Los valores de FIQ y BDI estuvieron significativamente alterados en los pacientes con FM, en comparación con los de los controles (FIQ, 70 ± 25 versus 12 ± 12, p < 0.0001; BDI, 17 ± 11 versus 4 ± 3, p < 0.0002). Solo cinco de 15 sueros de pacientes con FM tuvieron AANeu dirigidos específicamente contra las neuronas del núcleo vestibular medio del tronco encefálico; estos no se detectaron en los 14 sueros de los controles. Los AANeu reconocieron una proteína de 45 kDa. Conclusiones: El 30 % de los pacientes con FM tiene AANeu no descritos antes. Será necesario evaluar la inmunorreactividad antineural en una muestra más grande y determinar el papel de los AANeu en la fisiopatología de la FM.

Abstract Introduction: Fibromyalgia (FM) is a non-degenerative syndrome characterized by generalized, chronic musculoskeletal pain, as well as mood, memory and sleep disorders. Objective: To search for serum anti-neural antibodies (ANeuA) in patients with FM (FMP) in order to rule out autoimmune etiology. Methods: The Fibromyalgia Impact Questionnaire (FIQ) and BECK’s depression inventory (BDI) were applied. Immunorreactivity and the target recognized on the sera from FMPs and healthy subjects were analyzed by indirect immunofluorescence and Western blot. Results: Both FIQ and BDI values were significantly altered in FMPs in comparison with those of controls (FIQ, 70 ± 25 vs. 12 ± 12, p < 0.0001; BDI, 17 ± 11 vs. 4 ± 3, p < 0.0002). Only five out of 15 FMP sera had ANeuA specifically directed against neurons from the medial vestibular nucleus of the brainstem. This immunoreactivity was not detected in the sera from the 14 controls. ANeuA recognized a 45 kDa protein. Conclusions: 30% of FMPs have ANeuA that have not been described before. In future studies, it will be necessary for anti-neural immunoreactivity to be determined in a larger sample and for the role of ANeuAs in the pathophysiology of FM to be established.

Application of Tetrode Technology for Analysis of Changes in Neural Excitability of Medial Vestibular Nucleus by Acute Arterial Hypotension / 대한평형의학회지

OBJECTIVES: Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. METHODS: Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. RESULTS: Two or 3 types of unit could be classified according to the morphology of spikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. CONCLUSIONS: Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension.

Anatomy and Physiology of the Autonomic Nervous System / 대한평형의학회지

The autonomic nervous system (ANS) integrates the function of the internal organs for the homeostasis against various external environmental changes. The efferent components of the ANS are regulated by sensory signals arising from the viscera as well as non-visceral organs. The central neural networks that integrate these sensory signals and modify visceral motor output are complex, and synaptic reflexes formed in the brainstem and spinal cord integrate behavioral responses and visceral responses through the central neural networks. A detailed understanding of the neural network presented above may explain the role of the vestibular system on the homeostasis more extensively.

Expression of Metabotropic Glutamate Receptors in the Medial Vestibular Nucleus Following Acute Hypotension in Rats / 대한평형의학회지

BACKGROUND AND OBJECTIVES: Acute hypotension induces expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK), and glutamate release in the vestibular nuclei. Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. In this study, the signaling pathway of glutamate in the vestibular nuclei following acute hypotension was investigated. MATERIALS AND METHODS: Expression of metabotropic glutamate receptors (mGluRs) was measured by Western blotting in the medial vestibular nucleus following acute hypotension in rats. RESULTS: Expression of pGluR1 Ser831, a subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, peaked at 30 minutes after acute hypotension insult, and expression of pNR2B, a subtype of N-methyl-D-aspartate (NMDA) receptors, peaked at 2 hours after acute hypotension insult. Acute hypotension induced expression of Homer1a and group I mGluR in the medial vestibular nucleus. Expression of mGluR1 and mGluR5 peaked at 6 hours following acute hypotension insults. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors, resulting from acute hypotension insult, are transmitted through group I mGluRs as well as AMPA and NMDA receptors in the vestibular system.

Roles of Metabotropic Glutamate Receptors 1 and 5 in Rat Medial Vestibular Nucleus Neurons

Using whole cell current- and voltage-clamp recording we investigated the characteristics and pharmacology of group I metabotropic glutamate receptor (mGluR)-mediated responses in rat medial vestibular nucleus (MVN) neurons. In current clamp conditions, activation of mGluR I by application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced a direct excitation of MVN neurons that is characterized by depolarization and increased spontaneous firing frequency. To identify which of mGluR subtypes are responsible for the various actions of DHPG in MVN, we used two subtype-selective antagonists. (S)-(+)-alpha-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist that is selective for mGluR5. In voltage clamp conditions, DHPG application increased the frequency of spontaneous and miniature inhibitory postsynaptic currents (IPSCs) but had no effect on amplitude distributions. Antagonism of the DHPG-induced increase of miniature IPSCs required the blockade of both mGluR1 and mGluR5. DHPG application induced an inward current, which can be enhanced under depolarized conditions. DHPG-induced current was blocked by LY367385, but not by MPEP. Both LY367385 and MPEP antagonized the DHPG-induced suppression of the calcium activated potassium current (IAHP). These data suggest that mGluR1 and mGluR5 have similar roles in the regulation of the excitability of MVN neurons, and show a little distinct. Furthermore, mGluR I, via pre- and postsynaptic actions, have the potential to modulate the functions of the MVN.

THE EXPRESSION OF FOS IN THE WHOLE BRAIN OF RATS FOLLOWING COMPLEX DOUBLE ROTATION ON TWO AXES / 神经解剖学杂志

To investigate the relationship of the rotation stimulation with motion sickness, the expression of Fos protein in the whole brain of the rat stimulated by complex double rotation on two axes was observed in the present study. The rats were randomly divided into four groups: normal contral group; double-axes rotation stimulation group; the bilateral labyrinthectomy group; group of two-axes rotation stimulation after the bilateral labyrinthectomy. Immunohistochemical staining method was used to detect the expression of Fos protein in different regions of whole brain of the rat. The present results showed that: (1) No Fos-like immunoreactivity was detected in the brain of the rats in control group and the bilateral labyrinthectomy group; (2) In the double-axes rotation stimulation group, the Fos-like immunoreactive neurons were observed in many regions of the brain and brainstem of the rats following complex double-axes rotation stimulation, and the Fos-immunoreactivities were expressed in the nucleus. These Fos-immunopositive neurons were intensively distributed in different subnuclei of the vestibular nucleus complex (including medial, superior and spinal nuclei), nucleus of the solitary tract, locus coeruleus, medial and lateral parabrachial nucleus of the brainstem, paraventricular nucleus of the diencephalons and the amygdala of the limbic system; (3) The expression of Fos protein can be scarcely detected around forementioned regions in brains of the rats following complex two-axes rotation stimulation after the bilateral labyrinthectomy. The present results suggest that the double-axes rotation stimulation can activate effectively the vestibular neurons and many neurons of other region of the brain and brainstem are further activated through direct or indirect connections with vestibular nuclei after complex double rotation stimulation. These activated neurons may be related to the complex mechanism of the motion sickness.

Effects of S-nitroso-N-acetylpenicillamine on the Neuronal Excitability of the Medial Vestibular Nuclear Neuron

BACKGROUND: The medial vestibular nucleus is the largest one among the vestibular nuclei and known to play important roles not only in normal vestibular information processing but also in vestibular compensation. Glutamate is known to have a key role in vestibular compensation via long term potentiation and depression. But the action of nitric oxide related with glutamate is poorly studied. This experiment was designed to explore the effects of nitric oxide on the neuronal activity of a rat medial vestibular nuclear neuron using a nitric oxide enhancing drug, S-nitroso-N-acetylpenicillamine (SNAP). METHODS: Experiments were carried out on Sprague-Dawley rats aged 14 to 17 days. Neurons of MVN were obtained via enzymatic dissociation of a microtomized rat brainstem. Whole-cell membrane potentials were recorded at room temperature by using standard patch-clamp techniques. Action potentials were obtained after administration of SNAP. Changes of potassium currents were recorded using SNAP and ODQ (1H-[1, 2, 4] oxadiazolo [4, 3-a] quinozalin-1-one), an inhibitor of guanylyl cyclase. RESULTS: The mean spike frequency of action potentials was increased by adding SNAP. The mean amplitude of afterhyperpolarization was decreased by adding SNAP. The mean potassium current of medial vestibular nuclear neurons was decreased by SNAP. ODQ inhibited the SNAP-induced potassium currents. CONCLUSIONS: These results suggest that nitric oxide increases the neuronal activity of rat medial vestibular nuclear neurons by inhibiting potassium currents via a cGMP dependent mechanism.

Effects of Phenylephrine on the Excitability of Medial Vestibular Nuclear Neurons in Rats

Coeruleo-vestibular pathway which connects locus coeruleus and vestibular nuclei is noradrenergic. This study was designed to elucidate the effects of phenylephrine on the spontaneous activity of acutely isolated medial vestibular nuclear neurons of rat by whole-cell patch-clamp technique. Sprague-Dawley rats, aged 14 to 16 days, were used. After enzymatic digestion, dissociated medial vestibular neurons were transferred to a recording chamber mounted on an inverted microscope, and spontaneous action potentials were recorded by standard patch-clamp techniques. In current-clamp mode, the frequency of spontaneous action potential of medial vestibular nuclear neurons was decreased by phenylephrine (n=15). Phenylephrine increased the amplitude of afterhyperpolarization without changes in the resting membrane potential and spike width. In voltage-clamp mode, the whole potassium currents of the medial vestibular nuclear neurons were increased by phenylephrine (n=12). These experimental results suggest that alpha-receptor mediates the inhibitory effects on the neuronal activity of the medial vestibular nuclear neuron.

Inhibitory Effects of Norepinephrine on the Potassium Current of Rat Medial Vestibular Nuclear Neurons

BACKGROUND: This study aimed to explore the effects of norepinephrine on the potassium currents of rat medial vestibular nuclear neurons by using the whole-cell patch clamp technique. METHODS: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the portion of the medial vestibular nucleus neurons were obtained by micropunching. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and potassium currents were recorded by standard patch-clamp techniques under voltage-clamp modes. RESULTS: Norepinephrine inhibited the whole potassium currents of the medial vestibular nuclear neurons. Outward potassium currents were more suppressed in 4 mM 4-aminopyridine and norepinephrine added solutions than 4 mM 4-aminopyridine only, but were not suppressed in 10 mM tetraethylammonium and norepinephrine added solutions compared to 10 mM tetraethylammonium only. CONCLUSIONS: These results suggest that norepinephrine blocks the delayed rectifier potassium channels in medial vestibular nuclear neurons.

Expression of Immediate-Early Gene Proteins by Transient Occlusion of Anterior Inferior Cerebellar Artery in Vestibular Nuclei of Sprague-Dawley Rats

BACKGROUND: Anterior cerebellar artery (AICA) occlusion results in vestibular dysfunctions because the AICA supplies the vestibular nuclei (VN) in the brain stem as well as the peripheral vestibular organs in the inner ear. The purpose of this study was to evaluate the expression of immediate-early gene products, a metabolic marker of neural excitation in neurons, by AICA occlusion in the VN of Sprague-Dawley rats. METHODS: After chloral hydrate anesthesia all animals were subjected to unilateral AICA occlusion by using a microsurgical clamp for 30 min to induce a transient ischemia. Unilateral labyrinthectomy was chemically undertaken to eliminate vestibular afferent activity. Immunohistochemical staining and image analysis for cFos, FosB, Krox-24, and JunB proteins were performed 2 hours after AICA occlusion. RESULTS: There was a high expression of cFos protein in the bilateral medial and inferior VN 2 hours after AICA occlusion. AICA occlusion induced minimal changes in cFos protein expression in the lateral and superior VN. Mild to moderate expressions of FosB and JunB protein in VN was observed 2 hours after ischemic injury of the brain stem and inner ear. On the contrary, the number of cFos and FosB immunoreactive neurons significantly decreased in the medial vestibular nucleus ipsilateral to the injured labyrinth 2 hours after AICA occlusion in the UL group. CONCLUSIONS: These results suggest that ischemic afferent activity from the peripheral vestibular apparatus is essential for the expression of immediate-early gene products in the medial and inferior VN of rats following AICA occlusion.

Excitatory Effects of 5-Hydroxytryptamine on the Resting Activity of Medial Vestibular Nuclear Neurons in the Rat / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of 5-Hydroxytryptamine (5-HT) on the spontaneous activity of medial vestibular nuclear neurons of the rat. MATERIALS AND METHOD: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the brainstem portion of medial vestibular nuclear neuron was obtained by micropunching. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and spontaneous action potentials were recorded by standard patch-clamp techniques. RESULTS: The response of medial vestibular nuclear neurons to 5-HT applied in the recording chamber was not uniform. The spontaneous action potentials were increased in 10 cells, decreased in 3 cells and not altered in 2 of 15 cells. The spike width of the neurons was not affected by 5-HT. The spike frequency and resting membrane potential of these cells were increased by 5-HT. The depth of afterhyperpolarization was decreased by 5-HT. CONCLUSION: These results suggest 5-HT increases spontaneous firing of the medial vestibular nuclear neurons by altering the afterhyperpolarization.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

Extracellular regulated protein kinase1/2 (pERK1/2) is one of the major regulatory factors for transcription of the c-fos oncogene in neurons. The purpose of this study was to evaluate the expression of phosphorylated ERK1/2 within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following the acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2 in these nuclei occurred within 5 min after hemorrhage. However, in bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. Western blot confirmed the effect of bilateral labyrinthectomy on pERK1/2 protein expression in the medial vestibular nucleus 5 min after hemorrhage. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of ERK 1/2 in the VN.

Activation of Vestibular Neurons Projecting to Autonomic Brain Stem Nuclei Following Acute Hypotension in Rats

The purpose of the present study was to elucidate the possible involvement of the medial vestibular nucleus (MVN) and inferior vestibular nucleus (IVN) following acute hypotension in the vestibulo- autonomic reflex through vestibulosolitary or vestibuloventrolateral projections. Acute hypotension- induced cFos expression was assessed in combination with retrograde cholera toxin B subunit (CTb) tract tracing. After injection of CTb into the solitary region, CTb-labeled neurons were located prominently around the lateral borders of the caudal MVN and medial border of the IVN. The superior vestibular nucleus also had a scattered distribution of CTb-labeled neurons. After injection of CTb toxin into the unilateral VLM, the distributions of CTb-labeled neurons in the MVN and IVN were similar to that observed after injection into the solitary region, although there were fewer CTb-labeled neurons. In the caudal MVN, about 38% and 13% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. In the IVN, 14% and 7% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. Therefore, the present study suggests that acute arterial hypotension may result in activation of vestibulosolitary pathways that mediate behavioral and visceral reflexes, and vestibuloventrolateral medullary pathways that indirectly mediate vestibulosympathetic responses.

Actions of Orphan Opioid on the Membrane Conductances and Synaptic Transmission in Rat Medial Vestibular Nucleus Neurons

BACKGROUND: The medial vestibular nucleus (MVN) is involved in the reflex control of the head and eyes, and the recovery of vestibular function after vestibular injuries. This study was performed to investigate the actions of the orphan opioid (nociceptin) on the membrane conductances and synaptic transmission in rat MVN neurons. METHODS: Whole cell patch clamp recordings were carried out in the brainstem slice of neonatal rats. RESULTS: Nociceptin (2 micro M) inhibited the spontaneous discharge in the majority (83%) of MVN neurons. This inhibition was insensitive to the non-specific opioid receptor antagonist naloxone (10 micro M), but was effectively antagonized by the selective opioid receptor-like 1 (ORL1) receptor antagonist, [Nphe1] nociceptin(1-13)NH2 (3 micro M). Nociceptin had no effect on the rate or amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Nociceptin induced an outward current, and which was blocked by [Nphe1] nociceptin(1-13)NH2 in MVN neurons. Outward current reversed at -81 +/- 2 mV, which was close to the K+ equilibrium potential as calculated by the Nernst equation in 6 mM extracellular potassium solution. This indicates that the action of nociceptin involves postsynaptic receptors on the MVN neurons. CONCLUSIONS: These results suggest that nociceptin modulate neuronal excitability by activating a K+ conductance in postsynaptic neurons, not by modulation of synaptic transmission in MVN neurons.

Inhibitory and Excitatory Postsynaptic Currents of Medial Vestibular Nucleus Neurons of Rats

The medial vestibular nucleus (MVN) neurons are controlled by excitatory synaptic transmission from the vestibular afferent and commissural projections, and by inhibitory transmission from interneurons. Spontaneous synaptic currents of MVN neurons were studied using whole cell patch clamp recording in slices prepared from 13- to 17-day-old rats. The spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly reduced by the GABAA antagonist bicuculline (20micrometer), but were not affected by the glycine antagonist strychnine (1micrometer). The frequency, amplitude, and decay time constant of sIPSCs were 4.3 0.9 Hz, 18.1 2.0 pA, and 8.9 0.4 ms, respectively. Spontaneous excitatory postsynaptic currents (sEPSCs) were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466 (50micrometer) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. The AMPA mediated sEPSCs were characterized by low frequency (1.5 0.4 Hz), small amplitude (13.9 1.9 pA), and rapid decay kinetics (2.8 0.2 ms). The majority (15/21) displayed linear I-V relationships, suggesting the presence of GluR2-containing AMPA receptors. Only 35% of recorded MVN neurons showed NMDA mediated currents, which were characterized by small amplitude and low frequency. These results suggest that the MVN neurons receive excitatory inputs mediated by AMPA, but not kainate, and NMDA receptors, and inhibitory transmission mediated by GABAA receptors in neonatal rats.

Roles of Metabotropic Glutamate Receptors in Inhibitory Synaptic Transmission in Rat Medial Vestibular Nucleus Neurons

BACKGROUND: The medial vestibular nucleus (MVN) is involved in the reflex control of the head and eyes, and the recovery of vestibular function after vestibular lesions. This study was performed to investigate the characteristics of inhibitory postsynaptic currents (IPSC) and the roles of metabotropic glutamate receptors on inhibitory synaptic transmissions. METHODS: Whole cell patch clamp recordings were carried out from MVN neurons in brainstem slice of neonatal rats. RESULTS: The frequency and amplitude of the IPSC were significantly reduced by GABAA a n t a g o n i s t bicuculline (20 microM) but were not affected by the glycine antagonist strychnine (1 microM). The baseline frequency, amplitude and decay time constant of spontaneous IPSC (sIPSC) were 4.9+/-1.8 Hz, 25.9+/-3.1 pA, 8.7+/-0.5 ms, respectively. Glutamate (1 mM) increased the frequency of sIPSC, but decreased that of the miniature IPSC (mIPSC) in MVN neurons. Such dual effects of glutamate were mimicked by group I, II metabotropic glutamate receptor (mGluR) agonist ACPD (20 microM). The specific mGluR 2, 3 agonist DCG-IV (3 microM) reduced mIPSC frequency, but did not increase sIPSC frequency. The mGluR 1, 5 agonist DHPG (100 microM) increased sIPSC and mIPSC frequency. CONCLUSIONS: These data suggest that the IPSC recorded from MVN neurons are mediated mainly by GABAA receptors and glutamate-induced modulations of inhibitory synaptic transmissions can influence the excitability of MVN neurons.

Spatio-temporal Changes on c-Fos Protein Expression in the Brain Stem Nuclei following Arsanilate-induced Unilateral Labyrinthectomy in Rats

Spatio-temporal changes on c-Fos protein expression were investigated in vestibular compensation following unilateral labyrinthectomy (UL) induced by injection of arsanilate into the middle ear cavity, chemical labyrinthectomy, or surgical labyrinthectomy in medial vestibular nuclei (MVN), prepositus hypoglossal nuclei (PrH), and inferior olivary nuclei (ION) of Sprague-Dawley rats. Number of spontaneous nystagmus in surgical labyrinthectomy group was 28.2+/-.2 beats/10 sec at post-op 2 hs and the nystagmus disappeared 76 hs after UL. In chemical labyrinthectomy group, spontaneous nystagmus occurred 6 hs after UL and increased up to maximum at 12 hs and disappeared 96 hs. Head deviation in surgical labyrinthectomy group reached a peak at post-op 2 hs and recovered to control level at 144 hs, but chemical labyrinthectomy produced head deviation 24 hs after UL and increased degree of the deviation over time till 144 hs. Expression of c-Fos protein in surgical labyrinthectomy group at post-op 2 hs was 81+/-9.4 cells in ipsilateral MVN to the lesion side and 212+/-0 cells in contralateral MVN, which showed severe asymmetry between bilateral MVN, and decrease of c-Fos protein expression was more in contralateral MVN than in ipsilateral MVN at 6 hs. Chemical labyrinthectomy expressed more c-Fos protein in contralateral MVN 6 hs after UL and in ipsilateral MVN 12 hs after UL, which showed asymmetry of c-Fos protein expression between bilateral MVN. And the expression in ipsilateral MVN of chemical labyrinthectomy group was increased gradually 48 hs after UL and reached a peak at 72 hs. In chemical labyrinthectomy group, expression of c-Fos protein in PrH was increased more in ipsilateral than in contralateral 6 hs after UL and more in contralateral 12 hs after UL, and ION showed more expression of c-Fos protein in contralateral than in ipsilateral 6 hs after UL through 72 hs. These results suggest that the course of vestibular compensation and the temporal expression of c-Fos protein in the brain stem nuclei following UL differed between surgical and chemical labyrinthectomy.

Immunohistochemical Identification of Phosphorylated Extracellular Signal-Regulated Kinase1/2 in Rat Vestibular Nuclei by Unilateral Labyrinthectomy

This study evaluated the expression of phosphorylated signal-regulated kinase1/2 (pERK1/2), which is one of the main factors regulating transcription of the cfos oncogene in neurons, in the vestibular nuclei of Sprague-Dawley rats following unilateral labyrinthectomy (UL). Surgical UL was performed to eliminate afferent signals from the peripheral vestibular receptors in the inner ear, under a surgical microscope, 2 hours after anesthesia. Significant numbers of pERK1/2 immunoreactive neurons were seen in the superior, medial, and inferior vestibular nuclei. There were more pERK1/2 immunoreactive cells in the vestibular nuclei contralateral than in the vestibular nuclei ipsilateral to the injured labyrinth, which resulted in significant asymmetric expression of pERK1/2 immunoreactive cells. Subsequently, the pERK1/2 immunoreactivity decreased rapidly, disappearing 90 min after labyrinthectomy. No pERK1/2 labeling was seen in the lateral vestibular nucleus. These results suggest that intracellular signal pathways for the activation of extracellular signal-regulated kinase in the vestibular nuclei are involved in lesion-neural plasticity in the vestibular system

Responses of Inferior Olive Neurons to Stimulation of Semicircular Canals

In spite of abundant anatomical evidences for the fiber connection between vestibular nuclei and inferior olivary (IO) complex, the transmission of vestibular information through the vestibulo- olivo-cerebellar climbing fiber pathway has not been physiologically established. The aims of the present study were to investigate whether there are IO neurons specifically responding to horizontal rotation and also in which subregions of IO complex these vestibularly-activated neurons are located. The extracellular recording was made in 68 IO neurons and responses of 46 vestibularly-activated cells were analyzed. Most of the vestibularly-activated IO neurons responded to signals of vertical rotation (roll), while a small number (13/46) of recorded cells were activated by horizontal canal signal (yaw). Regardless of yaw-sensitive or roll-sensitive, vestibular IO neurons were excited, when the animal was rotated to the side contralateral to the recording side. The gain and excitation phase were very similar to otolithic or vertical-canal responses. Histologic identification of recording sites showed that most of vestibular IO neurons were located in beta subnucleus. Electrical stimulation of a HSC evoked an inhibitory effect on the excitability of the ipsilateral IO neurons. These results suggest that IO neurons mainly in the beta subnucleus receive vestibular signals from semicircular canals and otolithic organs, encode them, and transmit vestibular information to the cerebellum.

Auditory Auras in Complex Partial Epilepsy: Correlation of EEG and MRI Findings / 대한간질학회지

BACKGROUND: Auditory auras are rare but may have localizing value in patients presenting with epilepsy. We conducted the study to correlate the clinical characteristics, EEG and MRI findings in patients with auditory auras. METHODS: We identified 44 epileptic patients (23 male, 21 female) with auditory auras from Yonsei epilepsy registry between 1989 and 2000. All had routine EEG and MRI. These patients were subjected for the classification of lobar epilepsies based on the clinical-EEG-MRI correlations, which aimed at demonstrating 1) the association of auditory auras with temporal lobe epilepsy and 2) the localizing value of auditory auras to the neocortical temporal lobe epilepsy. RESULTS: Auditory auras were elementary in twenty-three, complex in eighteen, and both in three. Twenty patients described auditory aura only, and 24 patients described other associated auras including cephalic sensation, emotional, experiential, autonomic, epigastric, visual, vestibular, and somatosensory phenomena. The classification based on the Clinic-EEG-MRI correlations revealed that 33 of 44 patients (75%) were classified as temporal lobe epilepsy, however, it did not suggest any strong correlations with neocortical temporal lobe epilepsy. CONCLUSION: Auditory aura was strongly related with the temporal lobe epilepsy but it did not provide any further localizing value of seizure origin in patients with TLE.